Asthma is a chronic inflammatory disease of the airways characterized by contraction of airway smooth muscle due to actions of multiple local bronchoconstrictive substances. The syndrome affects ˜300 million individuals worldwide and is a substantial international health care burden. The inflammatory component of asthma is typically treated with corticosteroids, while the bronchoconstriction is treated with β-agonist bronchodilators, which as a class are the most prescribed therapeutic regimen for asthma treatment worldwide. Hence, the most commonly employed pharmacological treatment regimen indicated for asthma is co-administration of a bronchodilator and a corticosteroid. Significantly, however, corticosteroids are usually not indicated for intermittent asthma.
Problematically, the clinical response to β-agonists in the treatment of asthma displays a high degree of inter-individual variation that is not readily reconciled by clinical characteristics or baseline lung function. A significant fraction of patients appear to obtain no objective or subjective improvement with β-agonists, particularly when administered on a regularly scheduled regimen. Indeed, a recent analysis has estimated that ˜60% of the population variance in the forced expiratory volume in one second (FEV1) response to albuterol (a relatively selective Beta2-adrenergic bronchodilator and the active ingredient in PROVENTIL HFA) can be attributed to genetic variation. See Drazen, J. M., Silverman, E. K. and Lee, T. H. (2000) “Heterogeneity of therapeutic responses in asthma,” Br. Med. Bull., 56, 1054-1070.
Therefore, further delineating the genetic basis of β-agonist responsiveness based on the role of other key genes in the early portion of the signal transduction pathway provides a potential basis for understanding the inter-individual variation, and provides additional targets for pharmacological intervention. In view of the marked heterogeneity in response to the most common treatment regimen for asthma, and given that some forms of asthma, and certain other reversible bronchial obstruction disorders which operate at least partly through the same mechanisms, can be symptomatically acute and life-threatening, there is an urgent need in the art for rapid methods of determining whether a given patient will be responsive to certain treatment regimens. In addition there is a need for methods of screening populations of asthmatic and other reversible bronchial obstruction patients in order to identify individuals who will not benefit from treatment regimens that expose the patient to a risk of serious side effects. Further, there is a need to develop treatment regimens which account for the clinically observed inter-individual variation in β2AR agonist response and a need for the development of screening assays for pharmaceutical agents with bronchodilation efficacy in the population of asthma and/or reversible bronchial obstruction patients which do not respond optimally to conventional treatment.